The study of high frequency ventilation (HFV) and its use as a clinical tool has centered primarily on gas exchange and respiratory mechanics. The effects of high frequency ventilation on the control of breathing has received much less attention. HFV produces a slowing of breathing and apnea in patients, normal adult and neonatal humans and experimental animals. The apnea during HFV in experimental animals has been shown to be vagally mediated. However, the role of particular vagal afferents and respiratory muscle afferents remains in question. A systematic study of the ventilatory parameters most likely involved in the reflex apnea during HFV (stroke volume, frequency, CO2 and resting lung volume) has not been done. The experiments proposed herein will investigate the interaction of these four parameters in the respiratory reflex response to HFV. This will be done by independently varying each of the parameters to test for their effect on the apneic threshold. Once an apneic threshold has been defined, the relative contribution of vagal and muscle afferents to the response to HFV will be assessed. The results of these experiments will provide information that will be predictive in choosing a HFV ventilator setting that will elicite or avoid apnea in patients depending on the therapeutic regimen. A better understanding of the role of vagal and muscle afferents in the control of respiration will also result from these experiments.